I intend to illustrate how the unification of ideas derived from neurobiology and psychoanalysis can help to illuminate a very broad and diverse range of problems extending from traumatic memories to the repetition compulsion, the psychoanalytic theory of instinct and the concept of the self. It is not to much to hope that with a new synthesis of psychology, neurobiology and linguistics we are beginning to establish a biology of meaning. The physicist Murray Gell-Mann said that when "staircase are constructed between human psychology and biology, the best strategy is to work from the top down as well as from the bottom up". So that when we consider the interface between two disciplines such as psychoanalysis and neurobiology, there is no implication of reductionism.

This is not to imply that psychoanalysis and neurobiology are on all fours as the data obtained by means of the psychoanalytic method are selectively influenced by the personality of the observer and therefore cannot be reproduced in their entirety. However the same thing can be said for other disciplines such as anthropology whose data are also influenced by the observers personality. My position regarding the scientific status of psychoanalysis is therefore one of methodological pluralism, recognizing, at the same time, that psychoanalysis does not meet the positivists criteria of science. Psychoanalysis is a systematic method of observing the subjective state of the other, as the psychoanalyst is especially well placed to experience the affective interactions that occur between herself and the patient - what is commonly referred to as transference and countertransference. Psychoanalysis therefore provides a privileged access into human psychology , I cannot think of any other procedure that will yield this kind of knowledge. By means of this technique one can observe in microscopic detail the interplay of memory, affects and desire, all of which rest on the border between the brain and the mind.

What neurobiology has taught us is that memory is not analogous to a storehouse from which items are withdrawn. Memory is not a process of retrieval from some static memory bank because the brains memory is not like that of a computer with its permanent unchanging memory. What the brain stores is not simply isomorphic with perception because such a system would be functionally inefficient for over many years the accumulation of salient experiences would be a very large number indeed. Instead, we believe that what is retained is a memorial category of experience, retained as a latent potential that can be revived as an actual memory if current inputs re-evoke the original experience. One cannot claim that all memory is categorical, for as Schacter indicated in his recent overview of memory research, the brain generates several different kinds of memory systems. But as a psychoanalyst I am virtually certain that affective memory is categorical. Such memory is not only categorical but is also retranscriptive. The idea that memory is retranscriptive is not new as this observation was intuited by Freud in 1896 and by Sir Frederick Bartlett in 1932.

The relation between traumatic memories and psychopathology was the initial focus of Freuds investigation of hysteria that signaled the birth of psychoanalysis. Freud proposed that whether the memory of a trauma becomes pathogenic will be determined by the subsequent retranscription of that memory. This means that the effect of a trauma cannot be judged by the (reality) of the experience itself but will be determined by a subsequent process of translation. As Freud said: "Hysterics suffer mainly from reminiscences". Freud used the term nachträglichkeit to describe this process. His insight was as follows: memory is not isomorphic with experience; memory is not laid down once but several times over at the boundary of successive developmental epochs (see Freud letter to Fleiss December 6 1896 ,Masson 1985). At these boundaries a new transcription or translation takes place. Freud established here the particular quality of human temporality, the idea that human or psychological time is cyclic in contrast to the linear time of the physical world. Freud spoke of the retranscription of memory as a "translation" in which the development of the mind is subject to successive inscriptions where each developmental epoch translates the preceding one into a different idiom.

As I noted earlier, Sir Frederick Bartlett also intuited that memory was categorical and retranscriptive. I quote him: (cited by Freeman p. 23) "A new incoming impulse must become not merely a cue setting up a series of reactions all carried out in a fixed temporal order, but a stimulus which enables us to go directly to that portion of the organized setting of past responses, which is most relevant to the needs of the moment. "There is one way in which an organism could learn how to do this. It may be the only way... An organism has somehow to acquire the capacity to turn around upon its own "schemata" and to construct them afresh." The Nobel Laureate neurobiologist Gerald Edelman constructed a global theory of the functioning brain that proposes how this might be done. His theory is also one in which memory is both categorical and retranscriptive. Edelman suggests that what is stored in the brain is not something that has a precise correspondence with the original experience, but what is stored is a potentiality awaiting activation. The perceptual and motor apparatus serve memory by means of a scanning process in which there is an attempt to match current experience with old memory categories. What is stored in memory is not a replica of the event but the potential to generalize or refind the category or class of which the event is a member. To quote Edelman: "what is stored is stored is not replicative of the category or event, but is rather the capacity to generalize and then to narrow consequential behavior to achieve appropriate rewards. Recategorical memory is dynamic, transformational, and associative".

The neuroscientist Walter Freeman (1995) has also presented evidence that supports the concept of memory as a retranscription. He observed in EEG and direct brain recording in rabbits that the pattern of memory in response to specific odors is continually upgraded with subsequent exposures to new stimuli. Rabbits, no less than human beings are constructavists as they construct their world through interaction with the environment and are constantly upgrading their memory systems.

As a psychoanalyst I have observed that it is metaphor that mediates between current time, the here and now and the past. This is evident in cases of trauma as I shall illustrate. But before that I must say a few words about the concept of metaphor itself. As is true of affects and memory, metaphor also rests on the border between psychology and physiology, and as such represents an emergent property of mind. This is most evident in the process of dreaming for dreaming is an automatic neurophysiological event that generates predominately visual metaphors. As some of you may know metaphor is no longer viewed simply as a figure of speech but as George Lakoff has said "the locus of metaphor is not language at all but in the way we conceptualize one mental domain in terms of another; the locus of metaphor is thought not language". Linguists and cognitive scientists have recently emphasized that metaphor is both embodied and is a fundamental element of our cognitive processes. A scientist observed: "You dont see something until you have the right metaphor to let you perceive it." (quoted by Glieck p. 262). I believe that metaphor is the currency of mind. I have come to think of metaphor as a fundamental and indispensable structure of human understanding, a basic and irreducible unit of mental functioning. It is by means of metaphor that we generate new perceptions of the world; it is through metaphor that we organize and make sense out of experience. Metaphor has been defined as the mapping of one conceptual domain onto a dissimilar conceptual domain. For example consider the metaphor: sex is the poor mans opera. The pleasure we obtain from this metaphor rests upon the play of similarity and difference. Such metaphors are open and generative. There is another class of metaphor in which the meaning is relatively fixed or foreclosed. Such frozen metaphors have an important role in psychopathology as I will illustrate shortly. The essence of an open metaphor is the simultaneous appreciation of similarity and difference, whereas in a foreclosed metaphor, what is experienced is only a similarity and not a difference. The example that follows illustrates how a traumatic memory is cognitively evoked by such a foreclosed metaphor.

A patient who reported the following incident: Due to the fact that his airline went out on strike, he was stranded in a distant city and unable to return home. He did everything possible to obtain passage on another airline: he cajoled and pleaded with the functionaries of other airlines, all to no avail. Although my patient was usually not unduly anxious and was in fact a highly experienced traveler, who, in the past remained calm under circumstances that would frighten many people, in this particular situation he experienced an overwhelming and generalized panic. He felt as if the unyielding airline representatives were like Nazis and that the underground passages of the airline terminal resembled a concentration camp. The helplessness of not being able to return home, combined with the intransigence of the institutional authorities, evoked the following affective categorical memory. When this man was three years old he and his parents were residents of a central European country and, as Jews, were desperately attempting to escape from the Nazis. They did in fact manage to obtain an airline passage to freedom, but until that point the outcome was very much in doubt. In this example, his helpless inability to leave a foreign city combined with the intransigence of the authorities evoked a specific affect category. It would appear that the affective gestalt consisting of his helpless inability to leave plus the intransigence of the authorities was a metaphoric equivalent of the earlier trauma, a metaphoric equivalent that wedded the present to the past. This metaphorical correspondence triggered a global response in which the differences between the domains of past and present were obliterated. There was loss of the play of similarity and difference. The traumatic memory remained frozen as it was not subjected to the process of retranscription. Metaphor in this instance was foreclosed and not open and generative. This is some evidence that individuals who have been subjected to overwhelming trauma such as holocaust survivors lose their capacity to generate open metaphors. The lesson to be learned from psychic trauma is that memory, affects and metaphor form a unified synergistic system. The neurobiologic theory of the recontextualization of memory allows us to replace Freuds theory of the repetition compulsion. The novel aspects of experiences in real time are foreclosed and categorized as only a repetition of the past. That is to say, old affect categories are not recontextualized. If such memories are not recontextualized they will continue to exert an irresistible force. When one experiences the impetus to repeat painful experiences it does feel as if one is being driven by some internal force. But I would suggest that this force can be understood as the active component of memory rather than a derivative of instinct. The repetition of painful experiences is an essential mode of cognition. The urge to repeat represents an attempt to seek a perceptual identity between present and past objects, so that the memory of such unassimilated experiences exerts a selective influence upon our behavior and perceptions.

As I noted earlier, the interface between psychoanalysis and neurobiology operates from both the top down and from the bottom up; neurobiology is required for a deeper understanding of human psychology and vice-versa. Freud knew this when he attempted to ground his concept of instinct in evolutionary biology. In this sense he can be accurately described as a "Biologist of the Mind". Unfortunately however, his biology was that of the late nineteenth century and is now woefully out of date. This anachronism has contributed to a conceptual crisis within psychoanalysis for in Kuhns sense, psychoanalysis lost its organizing paradigm inasmuch as Freuds instinct concept was the cornerstone upon which his theory rested. Some psychoanalysts have attempted to preserve Freuds concept of instinct or drive by asserting that the instinct concept in psychoanalysis is a psychological concept and such is categorically different from the biological concept of instinct. But this argument does not seem to me to be convincing. Many psychoanalysts today simply reject the concept of instinct without proposing a convincing substitute explanation for human motivation. I hope to show how Gerald Edelmans theory of biologic value provides a hypothesis that is a viable substitute for Freuds outdated instinct theory.

As is true of individuals, words, concepts and categories have their own history. The term instinct, meaning to incite or impel, has had a long history in folk psychology before it was used as a scientific term. We are gradually recognizing the extent to which our folk concepts and categories have been influenced by certain philosophic assumptions which then become tacitly incorporated into scientific concepts. One such assumption is that instincts are distinct biologic categories. I have come to believe that such a view corresponds to a Platonic essentialist ideal. The essentialist ideal assumes that a category contains certain properties which makes it what it is, a uniform entity, a thing in itself defined by its "essence". Thinking in terms of platonic categories has had an unfortunate influence upon biology, for as Ernst Mayr has noted the pre-Darwinian idea of what constitutes a species was such an essentialist Platonic concept. Darwin himself used the term instinct but he intended that it denote behavior reflecting an evolutionary selectionist process rather than an entity.

I believe that Freud assumed this essentialist nature of instinct. For Freud, the "elementary" instincts were entities. Freud said (1923, p. 255): "Psychoanalysis early became aware that all mental occurrences must be regarded as built on the basis of an interplay of forces of the elementary instincts". His original classification of instincts proceeded along conventional lines, that is, along the line of a pre-existing folk psychology. He contrasted what he called the ego instincts, which included aggression and the instinct for self preservation, from the sexual instinct. Freud believed that he was supported in this classification by the contribution of the nineteenth century evolutionary biologist August Weismann (1834-1914) who contrasted the immortality of the germ plasm with all the other cells of the body that become extinct with the death of the individual. From the perspective of evolutionary biology, the ego instincts served the needs of the individual while the sexual instincts served the needs of the species. Therefore the conflict between sexual desire and self preservation reflected the deeper biological conflict in nature between the transitory need for the survival of the individual compared to the more lasting requirement of the survival of the species. Freud recognized however that this classification of instincts was provisional and will inevitably be modified by advances in biology. With his final classification of instincts as Eros and Thanatos in Beyond the Pleasure Principle, he admitted the uncertainty of his speculations. This uncertainty, he said, was increased by the necessity of borrowing from biology which he described as a "land of unlimited possibilities. We cannot guess what answers it will return in a few dozen years. They may be of a kind that will blow away the whole of our artificial structure of our hypotheses"

Freuds conventional classification of ego instincts and sexual instincts was later replaced, as you know, with a less conventional duality, that of Eros and Thanatos. Eros represented a unifying force whereas Thanatos, the death instinct, represented the tendency of all living things to revert back to an inanimate state. In this formulation he was expressing a kind of Goethe-like romantic biological theorizing. Today, few psychoanalysts believe in Freud's death instinct, but some psychoanalysts accept, what is in effect, a bowdlerized version of Freud's dual instinct theory. That is, they believe that sexuality and aggression are instinctual entities, independent forces that remain the transcendent element of all human motivation.

If instincts are the irreducible source of human motivation, it was logical for Freud to believe that affects were derived from instincts. Contemporary neurobiology has shown that Freud got things reversed. There is no scientific evidence for the existence of unitary instincts, there is no evidence that instincts are biological categories, whereas there is accumulating evidence that affects can be thought of as biologic categories because they can be differentiated in their neural pathways. Recent neurobiological research using non- invasive techniques on human subjects such as magnetic resonance scans (fMRI) on human subjects has produced data that indicate that such affects as anger, fear and pleasure can be differentiated by their separate neural pathways. For example it has been recently shown that the amygdala is specifically activated in human subjects as a response to seeing fearful faces. (Breiter et. Al) Neurobiology is now confirming what the psychologist Sylvan Tomkins intuited that affects not instincts or drives are the primary source of human motivation. To quote Tomkins: "Affects serve the purpose of a general amplifier in the motivational system, intensifying the drive which it accompanies. The seeming urgency of a drive state is a consequence of an affective response"

Affects can be thought of as markers of biologic value. Biologic value is a concept introduced by Gerald Edelman. It is a metaphor borrowed from economics analogous to the value we place upon material things. Edelman proposed in his theory of Neural Darwinism that in each species genetic constraints exert a selective influence upon memory, perception, and motivation. An animal, for example, may value light over darkness, warmth over cold and so forth. In our own species value can be thought of as a selective bias invoked by those brain structures that generate affects. The term value denotes those evolutionary constraints favoring behavior that fulfills homeostatic requirements or contributes to the inclusive fitness of the organism. Value therefore exerts a bias on memory perception and desire. As Edelman observed: current perceptions, which are value free, become meaningful through a value-driven past. This is consonant with the psychoanalytic observation that unconscious affective memories of the past endow the present with meaning and exert a selective influence on behavior. Those patients who are cut off from their inner affective life may experience the world as dead and without meaning. In the creation of meaning metaphor plays a salient role in that unconscious or implicit affective memories, find a cognitive metaphoric match or resonance in current perception and thus endow perception with meaning. From this perspective our perceptual categories are not in the world until we create them from within. If one accepts the hypotheses that affects are internal value-laden signals essential for survival, there is a clear progression from value, as an evolutionary property, to affects and meaning in the psychological domain.

The "biologic and social approaches to disordered minds" are referred to in this colloquium as poles, a connotation of opposites. I would rather think of the biologic and social domains as aspectual and synergistic rather than oppositional. As Clifford Geertz observed: "it should be possible to discuss the biological, psychological, sociological and cultural determinants of mans mental life concurrently without making any reductionist hypotheses". The necessity to consider both biologic and social determinants concurrently can be readily illustrated when one turn to the concept of the self. For one cannot think of the self without simultaneously considering biological, personal, social and cultural dimensions. The self is nearly co-terminus with consciousness in that it can be defined as a reflective consciousness. It is not surprising then that the controversies concerning the concept of self parallel those controversies concerning the subject of consciousness. Both the self and consciousness have been dismissed by some philosophers and cognitive scientists as mere epiphenomena. Some psychoanalysts also dismiss the idea of self, claiming on one hand that as it encompasses nearly everything that one experiences it is nearly meaningless, or that ones experience of self is simply a way of talking about the fantasies one has about oneself. Perhaps the best known philosopher who espoused the view that the self is only an epiphenomenon is David Hume. He described the mutability of the experience of the self as follows: "The soul does not remain unalterably the same, even for a moment. The mind is a kind of theater, where several perceptions successively make their appearance; pass, repass, glide away and mingle in an infinite variety of postures and situations". He concluded that there is no unity or continued identity to the self, and to believe in such a unity or continued identity of the self is simply the natural propensity of our imagination.

As a clinician I cannot accept the view that the self can be dismissed as a fantasy or that the sense of our continued identity is a figment of our imagination. I say this for the simple reason that if one is threatened with the loss of the sense of continuity and coherence of the self, this produces the most profound terror imaginable. Psychoanalysts have called this terror annihilation anxiety - a fear that the self is fragmenting and disintegrating. I believe that the sense of coherence and continuity of the self is a homeostatic process analogous to those processes that regulate our respiration and heart beat. William James, who is perhaps the foremost psychologist of the self, in The Varieties of Religious Experience relates an autobiographical episode in which he became terrified at the thought that he could be transformed into another person: "suddenly there fell upon me without any warning, just as if it came out of the darkness, a horrible fear of my own existence. Simultaneously there arose in my mind the image of an epileptic patient whom I had seen in the asylum, a black-haired youth with greenish skin, entirely idiotic, who used to sit all day on one of the benches, or rather shelves against the wall, with his knees drawn up against his chin, and the coarse grey undershirt, which was his only garment, drawn over them inclosing his entire figure. He sat there like a sort of sculptured Egyptian cat or Peruvian mummy, moving nothing but his black eyes and looking absolutely non-human. This image and my fear entered into a species of combination with each other. That shape am I, I felt potentially. Nothing that I possess can defend me against that fate, if the hour for it should strike me as it struck for him. There was such a horror of him, and such a perception of my own merely momentary discrepancy from him, that it was as if something hitherto solid within my breast gave way entirely, and I became a mass of quivering fear. After this the universe was changed for me altogether".

When James began to think about the nature of the self he was confronted with a central paradox: the self is nearly co-terminus with an ever changing consciousness yet the self, as ones identity, continues over time. James was all to well aware of the terror of losing ones sense of identity. If consciousness is ever changing how does one establish a unity between the past and present? In The Principles of Psychology he proposed a rather complicated analogy. He asked the reader to imagine a herd of cattle whose owner imposes unity by recognizing his own brand. But then how does this unity persist over time? James suggest that the "title" to the herd may be passed from one owner to the other as identity is transferred to a succession of selves over time. James later became dissatisfied with this analogy and felt that the paradox of consciousness and identity was nearly insoluble He was unable to reconcile how a momentary state of consciousness could connect with the stored memories of previous selves and create the unity that we experience as identity.

William James would have welcomed Edelmans theory that memory is both categorical and retranscriptive. For James analogy of the transfer of title through successive owners becomes less fanciful if it can now be thought of as the process of recategorization or retranscription of memory. The self, as is true of memory, can be analogized to a relatively persistent structure that undergoes continuous modification. From a global perspective, corresponding properties can be attributed to the brain. For the brain consists of pathways that are relatively hard wired which , in turn, are in constant flux and recombination. Coherence is superimposed through global binding mechanisms. From which we might infer that the sense of the coherence of the self is an analogous construction. (Singer).

An explicit neurobiologic theory of the self and consciousness was proposed by Gerald Edelman. This theory is linked to his concept of reentry. Reentry refers to the brains built-in coordinated signaling between anatomically separated structures that map both perceptual and conceptual categories. The brain reflectively maps its own mapping procedures - a neurologic correlate of consciousness of self. One does not have to posit a central inner agency or little man who directs these proceedings. Reentry is analogous to string quartet that is without a leader and yet whose members are exquisitely attuned to each other.

Edelman describes the self as a higher order of consciousness that enables the individual to create an internal model or schema of past, present and future. From an evolutionary perspective, this multi-layered or multi-leveled consciousness, confers a distinct adoptive advantage in that the individual is then free from the tyranny of events in real time. One might infer a principle that : a multi-layering of consciousness contributes to ones sense of autonomy and freedom.

Neurobiology supports the view that the brain is an organ, unlike any other, in that it is tailor-made for the individual. There are enormous variations within the central nervous system, both with regard to structure and function that cannot be attributed to genetic information. Even within the constraints of genetic instruction, the embryological development of the nervous system shows a remarkable degree of variability from the level of the cell to the level of global functioning. This variability results from a dynamic interaction with the environment. This means that genetically identical twins, even at birth, do not perceive the world identically; each person perceives the world uniquely, that is to say, every individual constructs their own reality. Modern science has confirmed what William Blake apprehended intuitively: "A fool sees not the same tree that a wise man sees". And as Oliver Sacks has said: "The nervous system adapts, is tailored, evolves so that experience, will, sensibility, moral sense, and all that one would call personality or soul becomes engraved in the nervous system. The result is that one's brain is one's own". So that in a certain sense we create ourselves. This view of self originating in neurobiology reinforces a view of human nature that is non-deterministic. This is a view of human nature that comes close to the philosophic pluralism expressed by Isaiah Berlin who views the human species as supremely inventive: a species that can fashion for itself a plurality of divergent natures.

Edelmans theory that the brains capacity to map its own procedures, an internal consciousness, results in a schema of past, present and future. This schema provides the individual with a measure of freedom from environmental inputs. This biological view of a self that is relatively autonomous is at variance with the certain sociological and psychoanalytic conceptions of the self that view the self not as relatively autonomous but exquisitely dependent. There is a general assumption that ones consciousness of self derives from the consciousness of the other person. This idea is contained in the sociological theories of George Herbert Mead who believed that the self is formed through experimental play in which one imitates or mirrors the role of the "generalized other". The belief that the self is formed through the consciousness of the other is also explicit in the theory of the self proposed by the psychoanalyst Heinz Kohut. Kohut who asserted that the coherence of the self is established through the empathic mirroring of the caretakers. Neurobiology has confronted us with another paradox - that self is both autonomous and dependent. I do not dispute that the self is formed through the consciousness of the other, without the consciousness of the other we are scarcely human. Yet it is also true that the self is a relatively autonomous emergent structure selecting from the culture that which is personally meaningful. We are, to a significant extent self created. Our sense of identify is both bestowed upon us and selected by us. As Charles Taylor has taught us in his wonderful book Sources of the Self, the language of the self is historically conditioned - the entire history of the culture can be found in the self. But Taylor also acknowledges that our identity is selective, our identity enables us to affirm what is important to us and what we value.

The literary critic Harold Bloom in his recent spiritual autobiography, Omens of Millennium provided a delightful example of how one selects from the culture that which will enable one to create oneself. He wrote: "at sixty-five, I find myself uncertain just when myself was born. I cannot locate it in my earliest memories of childhood, and yet I recall its presence in certain memories of reading, particularly of the poets William Blake and Hart Crane, when I was about nine or ten. In my instance at least, the self came to its belated birth (or second birth) by reading visionary poetry, a reading that implicitly was an act of knowing something previously unknown within me".

There is hope, as I have said, that working from the top down and the bottom up, through the unification of human psychology, cognitive science and neurobiology we will construct a new biology of meaning.